Nespelem is located on State Highway 155 on the Confederated Tribes of the Colville Indian Reservation.

Nespelem's name comes from an Indian word meaning "a beautiful valley between the hills." In 1910 the business district of Nespelem included a post office, a rooming house, hotel, meat market, livery barn and two general stores. Platted in 1913, the town was incorporated in 1934.

The Confederated Tribes of the Colville Reservation was established in 1872 though the 1.3 millsion acres that it eventually ended up with was about 1/3 the size of the original allocation. The land reductions were due in part ot public outcry by non-Indians to aurhorize mining claims in the 1870s, protests from ranchers, and opening up of the reservation to homesteading after 1916. Twelve tribes are represented on the reservation including the Colville, Nespelem, San Poil, Lakes, Palus, Wenatchi, Chelan, Entiat, Methow, Okanogan, Columbia (Sinkiuse), and Nez Perce.

Slolaskin Church (corner of Colville and Nez Perce Street), Colville Indian Agency off State Highway 155). Skolaskin's Church was built on the Colville Reservation in 1874 at Whitestone. Skolaskin was a powerful San Poil spiritual leader and medicine man who maintained the isolation of his people from the government, the Jesuit church and other Indian tribes. When Skolaskin returned from a U. S. government out-of-state detention facility in California, his influence had waned. Had it not been moved to tis present location around 1940, the log church would have been inudated under the waters of Lake Roosevelt.

Chief Joseph Memorial at the Nez Perce Cemetery (State Highway 155 on the Colville Reservation in Okanogan County). Chief Joseph sought to hold on to traditional Nez Perce lands in southeastern Washington, Oregon and north Idaho but he and many others were driven out of their homelands. The Nez Perce War of 1877 saw several battles with the U. S. Army, which eventually resulted in Joseph, Yellow Wolf and many followers making a historic 1700-mile trek and forced retreat through Oregon, Idaho, Whoming, Montana and into Canada. Joseph spent the remaining 27 years of his life on the Colville Reservation where he died September 21, 1904. Yellow Wolf, likewise, died here in 1935 and both are buried in the New Perce Cemetery above Nespelem. The Chief Joseph Memorial was placed on the National Register for Historic Places in 1974.